Over the last fifteen years, it has become possible to study theories of cognition with fMRI, using what are usually termed "activation studies." However, conventional fMRI studies give no direct information about signal transduction or the underlying neurochemistry. It would be a significant advance in the field of neuroimaging if activation studies could localize and identify specific neuronal populations (dopaminergic, opioid, serotonergic, etc.) involved in a cognitive task or behavior. In that regard, it is well known that cognitive activation increases neuronal firing rate, increasing the endogenous neurotransmitter level in the synapse. In principal, the transient increase in neurotransmitter level elicited by an activation task can be used to alter the binding kinetics of radioligands measured with PET. Studies using this paradigm have been performed in a few centers, with promising but not definitive results. Simultaneous scanning using a new combination MR/PET scanner offers the possibility of a more rational and rigorous approach to the mapping of neurotransmission. The goal of this application is to develop this methodology, making use of the new capability of PET/MR scanners and advanced processing methods to cross validate the PET/fMRI approach. The cross validation of the methodology will be performed with a primate model, using a stepwise strategy involving pharmaceutical challenge and well understood activation tasks that engage motor processing and motor planning. It will be important to make significant improvements in the methodology and to develop experimental designs most suitable for simultaneous MR/PET. "The goal of this project is to develop, demonstrate and validate methodology using PET/fMRI scanning which is capable of mapping neurotransmission in response to pharmaceutical, behavioral and cognitive stimuli. PUBLIC HEALTH RELEVANCE: Current brain imaging methods are sensitive to changes in blood flow and metabolism but they do not give direct information about the underlying neurochemistry. The goal of this project is to map the spatial distribution in the awake primate brain, using simultaneous MR/PET scanning.